We propose that hypertyraminemia of Reye's syndrome may contribute to the development of encephalopathy of this disease. Several observations made by us within the last five years support this hypothesis. The main objectives of this proposal are to identify the disorder of tyramine metabolism in Reye's syndrome and to determine the relationship of this disorder to the development of the encephalopathy of this disease. Two types of biochemical measurements will be carried out in patients with Reye's syndrome. First, measurement of tyramine, L-dopa, dopamine, norepinephrine and epinephrine in plasma, urine and ventricular fluid on admission, before treatment and following therapy until encephalopathy is resolved. Secondly, determination of monoamine oxidase (MAO) activity in hepatic biopsy specimen and blood platelets will also be made. Specifically, this proposal will address and attempt to answer two questions: l) What is the relationship between central hypertyraminemia and stage and duration of coma in Reye's syndrome? Is the adverse effect of central hypertyraminemia the culmination of cerebral edema and/or exacerbations caused by deficiencies in neuronal dopamine? 2) Is hypertyraminemia of Reye's syndrome a reflection of decreased hepatic or total mitochondrial monoamine oxidase activity? Consequently, what is the relationship of monoamine oxidase activity in liver to that in platelets? If a toxin affects mitochondrial MAO simultaneously in different tissues of patients with Reye's syndrome, then reduced platelet MAO activity, and enzyme under genetic control, may represent a genetic marker that may be used to identify those individuals who might be at risk to develop Reye's syndrome. In summary, the studies outlined in this proposal will help to identify the factors responsible for the encephalopathy of Reye's syndrome. Specifically, this will be accomplished by determining the role of impaired mitochondrial MAO activity and resultant hypertyraminemia in the pathogenesis of the hepatocerebral manifestations of this disease. Furthermore, the results of this study will also provide us with a better understanding of the recognition, management and treatment of this disease.